| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
The target is GRK5, with an IC50 of 0.02 μM; KR-39038 inhibits GRK5-mediated phosphorylation and, in neonatal cardiomyocytes, suppresses the HDAC5 pathway, thereby reducing angiotensin II–induced cellular hypertrophy and improving cardiac function in heart failure models.
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| ln Vitro |
HDAC5 phosphorylation and angiotensin II-induced neonatal cardiomyocyte hypertrophy are both markedly inhibited by KR-39038 (0-1.0 μM, 24 hours) [1].
KR-39038 inhibits GRK5 with IC50 = 0.02 μM; in neonatal rat cardiomyocytes, it significantly inhibits angiotensin II–induced cellular hypertrophy through suppression of the HDAC5 pathway at concentrations of 0–1.0 μM, and it shows anti-hypertrophic and cardioprotective activity in cellular models of heart failure. |
| ln Vivo |
KR-39038 (0-30 mg/kg, orally, once daily for 14 days) substantially lowers ventricular hypertrophy and dysfunction in experimental heart failure [1]. Pharmacokinetic characteristics of KR-39038 in Sprague-Dawley rats [1]. Parameter IV (5 mg/kg) PO (300 mg/kg) Cmax (μg/mL) NA 5.2 ± 2.8 Tmax (h) NA 0.7 ± 0.2 t1/2 (h) 0.7 ± 0.04 2.3 ± 2.9 AUC0-∞ (μg ) *h/mL) 3.4 ± 1.0 8.9 ± 5.0 CL (L/h/kg) 1.6 ± 0.5 NA Vss (L/kg) 1.2 ± 0.2 NA F (%) 4.3 ± 2.4
In vivo, KR-39038 is orally active and shows anti-myocardial hypertrophy effects and improved cardiac function in animal models of heart failure; it reduces angiotensin II–induced cardiac remodeling and HDAC5 pathway activation, supporting its investigation for heart failure therapy. |
| Enzyme Assay |
GRK5 kinase activity is measured by incubating recombinant GRK5 with an activated GPCR substrate or a synthetic peptide and [γ-32P]ATP in the presence of graded KR-39038 concentrations; phosphorylated substrate is quantified by scintillation counting or gel electrophoresis, and IC50 values are calculated; selectivity is assessed against other GRK family members.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: Primary neonatal cardiomyocytes (isolated from SD rats (1-2 days old) using primary cardiomyocyte isolation kit) Tested Concentrations: 0 μM, 0.03 μM, 0.1 μM, 0.3 μM, 1.0 μM Incubation Duration: 24 hrs (hours) Experimental Results: Cell hypertrophy induced by angiotensin II was Dramatically inhibited at concentrations of 0.1 μM and higher. Angiotensin II-induced HDAC5 phosphorylation is diminished at 0.3 µM and higher. Neonatal rat cardiomyocytes are treated with KR-39038 (0–1.0 μM) in the presence or absence of angiotensin II; cellular hypertrophy is measured by cell surface area, protein synthesis by leucine incorporation, HDAC5 phosphorylation and nuclear export by Western blotting and immunofluorescence, and fetal gene expression (ANP, BNP) by RT-qPCR. |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice ( Male, 20-24 g, transverse aortic coarctation) [1]
Doses: 30 mg/kg Route of Administration: Orally, one time/day for 2 weeks, starting 24 hrs (hrs (hours)) after surgery Experimental Results: 43% reduction in left ventricular weight, and Dramatically attenuated the development of cardiac hypertrophy. Animal/Disease Models: SD (SD (Sprague-Dawley)) rat (male, 380-420 g, coronary artery ligation) [1] Doses: 10 mg/kg, 30 mg/kg Route of Administration: Orally, one time/day for 12 weeks, Results one hour after surgery starting on the 24th: demonstrated significant preservation of cardiac function and attenuation of myocardial remodeling in a rat model of chronic heart failure after coronary artery ligation. Animal/Disease Models: SD rat[1] Doses: 5 mg/kg (intravenous (iv) (iv)injection), 300 mg/kg (oral) Route of Administration: intravenous (iv) (iv)injection or oral administration, single dose (pharmacokinetic/PK/PK analysis) Experimental Results: After intravenous (iv) (iv)injection The AUC∞ values of KR-39038 at 10 mg/kg and 300 mg/kg orally were 3.4 ± 1.0 and 8.9 ± 5.0 µg·h/mL, Rats or mice with angiotensin II–induced or pressure-overload cardiac hypertrophy receive KR-39038 by oral gavage at doses such as 0–30 mg/kg; cardiac function is assessed by echocardiography, heart weight/body weight ratio and cardiomyocyte cross-sectional area are measured histologically, and HDAC5 phosphorylation in heart tissue is quantified to confirm target engagement. |
| References |
| Molecular Formula |
C24H32CLFN6O
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|---|---|
| Molecular Weight |
475.001887321472
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| Exact Mass |
474.231
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| CAS # |
2770300-35-9
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| PubChem CID |
163404364
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| Appearance |
White to yellow solid powder
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
33
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| Complexity |
624
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C2=C(C=C(F)C(NCCCNCCCCNCCCN)=C2)C(=O)NC=1C1=CC=CC=C1Cl
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| InChi Key |
UEAYNKFJXGVWBQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H32ClFN6O/c25-19-8-2-1-7-17(19)23-31-21-16-22(20(26)15-18(21)24(33)32-23)30-14-6-13-29-11-4-3-10-28-12-5-9-27/h1-2,7-8,15-16,28-30H,3-6,9-14,27H2,(H,31,32,33)
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| Chemical Name |
7-[3-[4-(3-aminopropylamino)butylamino]propylamino]-2-(2-chlorophenyl)-6-fluoro-3H-quinazolin-4-one
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~115 mg/mL (~242.11 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1053 mL | 10.5263 mL | 21.0526 mL | |
| 5 mM | 0.4211 mL | 2.1053 mL | 4.2105 mL | |
| 10 mM | 0.2105 mL | 1.0526 mL | 2.1053 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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